Tissue engineering is an area of biomaterials research that combines cellular biology, engineering science and materials science to develop artificial tissues that may be used to repair or replace body tissues, such as bone, cartilage, blood vessels, bladder and skin. Recent developments in the field of tissue engineering have yielded novel tissue replacement strategies. Scientific advances in biomaterials, stem cells, growth and differentiation factors, and biomimetic environments have allowed the preparation of artificial tissues by combining engineered extracellular matrices, cells, and biologically active molecules. Among the major challenges now facing scientists is the development of laboratory-grown, structurally complex artificial tissues that are functionally and biomechanically stable and acceptable for transplantation procedures, since the artificial tissue must have specific mechanical and structural properties to function properly within the body.
In tissue engineering, cells are often implanted or “seeded” into an artificial structure capable of supporting three-dimensional tissue formation. These structures, typically called “scaffolds,” often play an important role, both ex vivo and in vivo, of reproducing the environment of cells in the body. Scaffolds usually serve at least one of the following purposes: allowing cell attachment and migration; delivering and retaining cells and biochemical factors; enabling diffusion of vital cell nutrients and expressed products; and/or exerting mechanical and biological influences to modify the behavior of the cellular phase.
Development of novel scaffolds for tissue engineering is an ongoing effort. The scaffold must be biocompatible, bioresorbable and mimic at least some of the structural and functional properties of the extracellular matrix. Additionally, much like their correlated tissue type, the scaffold must facilitate cell adhesion, allow tissue orientation and facilitate tissue functionality (Hutmacher et al., 2001, J. Biomed. Mat. Res. 55(2):203-16). Therefore, it is important to generate a three-dimensional scaffold that provides the mechanical properties of the native tissue (including its specific surface pattering), allowing cellular attachment, alignment and proliferation. As an example, myocardium is made up of thick collagen matrix with well-aligned myocytes that lead to mechanical anisotropy (Jawad et al., 2008, Br. Med. Bull. 87:31-47). To be useful in myocardial tissue engineering, an artificial scaffold must have properties that enable it to mimic or support the native myocardium.
In order to achieve the goal of tissue reconstruction, the scaffold of choice must meet specific requirements. The scaffold must have an adequate level of porosity to facilitate cell seeding and diffusion of both cells and nutrients throughout the whole structure. Biodegradability is often an essential characteristic of the scaffold since it should preferably be absorbed by the surrounding tissues without the necessity of surgical removal. The rate at which scaffold degradation occurs has to coincide as much as possible with the rate of tissue formation. While cells are fabricating their own natural matrix structure around themselves, the scaffold provides structural integrity within the body. The scaffold will eventually break down within the body, leaving behind the newly formed tissue, which will take over the mechanical load.
Various materials (natural and synthetic, biodegradable and permanent) have been investigated as scaffolds. Most of these materials were already employed as bioresorbable sutures. Examples of these materials are collagen and polyesters. New biomaterials have been engineered to have ideal properties and functional customization, such as injectability, manufacturing ease, biocompatibility, non-immunogenicity, transparency, appropriate density, and appropriate resorption rates. A commonly used synthetic material is PLA (polylactic acid), a polyester that degrades within the human body to form lactic acid, which is naturally removed from the body. Other materials are polyglycolic acid (PGA) and polycaprolactone (PCL). Their degradation mechanisms are similar to that of PLA, but they exhibit respectively a faster and a slower rate of degradation compared to PLA. Scaffolds may also be constructed from natural materials. In particular, various derivatives of the extracellular matrix (collagen, fibrin, polysaccharides such as chitosan, or glycosaminoglycans such as hyaluronic acid) have been studied to evaluate their ability to support cell growth.
There remains a need to identify novel scaffolds that may be used in tissue engineering. Such scaffolds should be easily prepared and have three-dimensional anisotropic nanofibrous structures, which mimic the intrinsically anisotropic network and three-dimensionality of the tissue that needs to be repaired or replaced. The present invention fulfills this need.